AGA Clinical Practice Update on the Diagnosis and Management of Extraesophageal Gastroesophageal Reflux Disease: Expert Review
Authors: Joan W. Chen, Marcelo F. Vela, Kathryn A. Peterson, Dustin A. Carlson
Journal: Clinical Gastroenterology and Hepatology (2023)

DescriptionThe purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available evidence and expert advice regarding the clinical management of patients with suspected extraesophageal gastroesophageal reflux disease.MethodsThis article provides practical advice based on the available published evidence including that identified from recently published reviews from leading investigators in the field, prospective and population studies, clinical trials, and recent clinical guidelines and technical reviews. This best practice document is not based on a formal systematic review. The best practice advice as presented in this document applies to patients with symptoms or conditions suspected to be related to extraesophageal reflux (EER). This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations.Best Practice Advice 1Gastroenterologists should be aware of potential extraesophageal manifestations of gastroesophageal reflux disease (GERD) and should inquire about such disorders including laryngitis, chronic cough, asthma, and dental erosions in GERD patients to determine whether GERD may be a contributing factor to these conditions.Best Practice Advice 2Development of a multidisciplinary approach to extraesophageal (EER) manifestations is an important consideration because the conditions are often multifactorial, requiring input from non-gastroenterology (GI) specialties. Results from diagnostic testing (ie, bronchoscopy, thoracic imaging, laryngoscopy, etc) from non-GI disciplines should be taken into consideration when gastroesophageal reflux (GER) is considered as a cause for extraesophageal symptoms.Best Practice Advice 3Currently, there is no single diagnostic tool that can conclusively identify GER as the cause of EER symptoms. Determination of the contribution of GER to EER symptoms should be based on the global clinical impression derived from patients' symptoms, response to GER therapy, and results of endoscopy and reflux testing.Best Practice Advice 4Consideration should be given toward diagnostic testing for reflux before initiation of proton pump inhibitor (PPI) therapy in patients with potential extraesophageal manifestations of GERD, but without typical GERD symptoms. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable.Best Practice Advice 5Symptom improvement of EER manifestations while on PPI therapy may result from mechanisms of action other than acid suppression and should not be regarded as confirmation for GERD.Best Practice Advice 6In patients with suspected extraesophageal manifestation of GERD who have failed one trial (up to 12 weeks) of PPI therapy, one should consider objective testing for pathologic GER, because additional trials of different PPIs are low yield.Best Practice Advice 7Initial testing to evaluate for reflux should be tailored to patients' clinical presentation and can include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy.Best Practice Advice 8Testing can be considered for those with an established objective diagnosis of GERD who do not respond to high doses of acid suppression. Testing can include pH-impedance monitoring while on acid suppression to evaluate the role of ongoing acid or non-acid reflux.Best Practice Advice 9Alternative treatment methods to acid suppressive therapy (eg, lifestyle modifications, alginate-containing antacids, external upper esophageal sphincter compression device, cognitive-behavioral therapy, neuromodulators) may serve a role in management of EER symptoms.Best Practice Advice 10Shared decision-making should be performed before referral for anti-reflux surgery for EER when the patient has clear, objectively defined evidence of GERD. However, a lack of response to PPI therapy predicts lack of response to anti-reflux surgery and should be incorporated into the decision process. The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available evidence and expert advice regarding the clinical management of patients with suspected extraesophageal gastroesophageal reflux disease. This article provides practical advice based on the available published evidence including that identified from recently published reviews from leading investigators in the field, prospective and population studies, clinical trials, and recent clinical guidelines and technical reviews. This best practice document is not based on a formal systematic review. The best practice advice as presented in this document applies to patients with symptoms or conditions suspected to be related to extraesophageal reflux (EER). This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Gastroenterologists should be aware of potential extraesophageal manifestations of gastroesophageal reflux disease (GERD) and should inquire about such disorders including laryngitis, chronic cough, asthma, and dental erosions in GERD patients to determine whether GERD may be a contributing factor to these conditions. Development of a multidisciplinary approach to extraesophageal (EER) manifestations is an important consideration because the conditions are often multifactorial, requiring input from non-gastroenterology (GI) specialties. Results from diagnostic testing (ie, bronchoscopy, thoracic imaging, laryngoscopy, etc) from non-GI disciplines should be taken into consideration when gastroesophageal reflux (GER) is considered as a cause for extraesophageal symptoms. Currently, there is no single diagnostic tool that can conclusively identify GER as the cause of EER symptoms. Determination of the contribution of GER to EER symptoms should be based on the global clinical impression derived from patients' symptoms, response to GER therapy, and results of endoscopy and reflux testing. Consideration should be given toward diagnostic testing for reflux before initiation of proton pump inhibitor (PPI) therapy in patients with potential extraesophageal manifestations of GERD, but without typical GERD symptoms. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable. Symptom improvement of EER manifestations while on PPI therapy may result from mechanisms of action other than acid suppression and should not be regarded as confirmation for GERD. In patients with suspected extraesophageal manifestation of GERD who have failed one trial (up to 12 weeks) of PPI therapy, one should consider objective testing for pathologic GER, because additional trials of different PPIs are low yield. Initial testing to evaluate for reflux should be tailored to patients' clinical presentation and can include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy. Testing can be considered for those with an established objective diagnosis of GERD who do not respond to high doses of acid suppression. Testing can include pH-impedance monitoring while on acid suppression to evaluate the role of ongoing acid or non-acid reflux. Alternative treatment methods to acid suppressive therapy (eg, lifestyle modifications, alginate-containing antacids, external upper esophageal sphincter compression device, cognitive-behavioral therapy, neuromodulators) may serve a role in management of EER symptoms. Shared decision-making should be performed before referral for anti-reflux surgery for EER when the patient has clear, objectively defined evidence of GERD. However, a lack of response to PPI therapy predicts lack of response to anti-reflux surgery and should be incorporated into the decision process. Gastroesophageal reflux disease (GERD) is increasing in prevalence, and this, in turn, implores increased investigation into its extraesophageal manifestations. Extraesophageal reflux (EER) is a subset of gastroesophageal reflux (GER) that leads to troublesome symptoms/conditions that are not normally attributed to the esophagus. Diagnostic algorithms for EER are difficult because the manifestations of EER are heterogeneous and often overlap with other conditions. The healthcare burden of EER is great because of the lack of a gold standard diagnostic test, poor responsiveness to proton pump inhibitor (PPI) therapy, and delay in recognition.1Katz P.O. Dunbar K.B. Schnoll-Sussman F.H. et al.ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease.Am J Gastroenterol. 2022; 117: 27-56Crossref PubMed Scopus (145) Google Scholar, 2Durazzo M. Lupi G. Cicerchia F. et al.Extra-esophageal presentation of gastroesophageal reflux disease: 2020 update.J Clin Med. 2020; 9Crossref PubMed Scopus (36) Google Scholar, 3Martinucci I. Albano E. Marchi S. et al.Extra-esophageal presentation of gastroesophageal reflux disease: new understanding in a new era.Minerva Gastroenterol Dietol. 2017; 63: 221-234PubMed Google Scholar, 4Vaezi M.F. Katzka D. Zerbib F. Extraesophageal symptoms and diseases attributed to GERD: where is the pendulum swinging now?.Clin Gastroenterol Hepatol. 2018; 16: 1018-1029Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar The concept of extraesophageal symptoms secondary to GERD is complex and often controversial, leading to diagnostic and therapeutic challenges. Several extraesophageal symptoms have been associated with GERD, although the strength of evidence to support a causal relation varies. Possible extraesophageal manifestations of GERD include cough, laryngeal hoarseness, dysphonia, pulmonary fibrosis, asthma, dental erosions/caries, sinus disease, ear disease, post-nasal drip, and throat clearing (Table 1). Patients with EER may not complain of heartburn or regurgitation; thus, the onus may lie on the clinician to determine whether acid reflux is a contributing factor of the symptoms. Causation (as opposed to association) is a difficult assessment because many conditions thought to be related to EER are associated with a higher incidence of acid reflux.2Durazzo M. Lupi G. Cicerchia F. et al.Extra-esophageal presentation of gastroesophageal reflux disease: 2020 update.J Clin Med. 2020; 9Crossref PubMed Scopus (36) Google ScholarTable 1Different Postulated Manifestations of EERExtraesophageal symptoms and manifestationsDifferential diagnosisMultidisciplinary teamLaryngeal/ENT Laryngitis/hoarseness Globus Mucus in throat Throat clearing Throat pain Sinus inflammation Post-nasal dripPostnasal dripLaryngeal allergyFunctional dysphoniaLaryngeal papillomaMuscle tension dysphoniaVocal cord paralysisVocal cord polypsSinusitis (occult)Gastric inlet patchOtolaryngologyGastroenterologyAllergy/ImmunologySpeech pathologyBehavioral psychologyPulmonary Asthma Chronic cough Pulmonary fibrosis Allograft failurePost-nasal dripAsthmaVocal cord dysfunctionMedication reaction (ie, angiotensin converting enzyme inhibitors)Lung transplant rejectionPulmonologyOtolaryngologyAllergy/ImmunologyGastroenterologyPrimary careDentition Dental erosions Dental cariesPoor dietary habits (ie, acidic soft drinks, fruit juices)Eating disorders with regurgitation (bulimia)Xerostomia (Sjogren's)Environmental (ie, around acidic fumes)DentistryGastroenterologyNutritionPrimary carePsychologyNOTE. Gastroenterologists should keep in mind all possible non-EER contributions to the symptoms and the potential multidisciplinary teams for collaborative evaluation. Open table in a new tab NOTE. Gastroenterologists should keep in mind all possible non-EER contributions to the symptoms and the potential multidisciplinary teams for collaborative evaluation. The difficulties in confirming a causal association between reflux and EER symptoms relate to variable responses to PPI therapy. Additional controversy arises over whether fluid refluxate causes damage leading to EER, whether the fluid needs to be acidic or merely contain pepsin, or whether neurogenic signaling leads to inflammation and subsequent symptoms.5Hom C. Vaezi M.F. Extra-esophageal manifestations of gastroesophageal reflux disease: diagnosis and treatment.Drugs. 2013; 73: 1281-1295Crossref PubMed Scopus (60) Google Scholar,6Zhang Z. Bao Y.Y. Zhou S.H. Pump proton and laryngeal H(+)/K(+) ATPases.Int J Gen Med. 2020; 13: 1509-1514Crossref PubMed Scopus (6) Google Scholar Thus, a simple trial of PPI may not provide accurate diagnostic information regarding the contribution of acid reflux to EER symptoms. Herein we will discuss conditions suspected to have potential relationships to acid reflux and best approaches to diagnosis, evaluation, and therapy. Best Practice Advice 1: Gastroenterologists should be aware of potential extraesophageal manifestations of gastroesophageal reflux disease (GERD) and should inquire about such disorders including laryngitis, chronic cough, asthma, and dental erosions in GERD patients to determine whether GERD may be a contributing factor to these conditions. Best Practice Advice 2: Development of a multidisciplinary approach to extraesophageal (EER) manifestations is an important consideration because the conditions are often multifactorial, requiring input from non-gastroenterology (GI) specialties. Results from diagnostic testing (ie, bronchoscopy, thoracic imaging, laryngoscopy, etc) from non-GI disciplines should be taken into consideration when gastroesophageal reflux (GER) is considered as a cause for extraesophageal symptoms. Most disorders suspicious for EER are often seen by specialties outside of gastroenterology such as pulmonary, otolaryngology, and dentistry. Patients with EER will commonly see many different physicians and undergo a multitude of testing without a final conclusive determination. A multidisciplinary approach with communication between all treating disciplines results in the best outcomes for suspected EER patients. Common disorders thought to have an association with EER are chronic cough, laryngeal hoarseness, dysphonia, pulmonary fibrosis, asthma, dental erosions, sinus disease, ear disease, post-nasal drip, voice dysphonia, and throat clearing. Table 1 lists conditions commonly attributed to EER, alternative diagnoses, and the multidisciplinary teams that can contribute to patient workup and management. Multiple respiratory conditions are postulated to be related to gastroesophageal reflux. The impact of esophageal dysfunction on pulmonary and laryngeal disorder is likely related to 2 different mechanisms: the reflux pathway leading to micro-aspiration and the reflex pathway triggering vagally mediated airway reactions.6Zhang Z. Bao Y.Y. Zhou S.H. Pump proton and laryngeal H(+)/K(+) ATPases.Int J Gen Med. 2020; 13: 1509-1514Crossref PubMed Scopus (6) Google Scholar In the reflux pathway, EER can exacerbate inflammatory conditions via acid or non-acid mechanisms, including micro-aspiration of other digestive fluids. In such situations, symptom improvement may not be seen with acid suppression. In the reflex pathway, EER may contribute to the pathology of supra-esophageal complaints by increasing laryngeal or airway inflammation via neurologic mechanisms.7Qiu Z. Yu L. Xu S. et al.Cough reflex sensitivity and airway inflammation in patients with chronic cough due to non-acid gastro-oesophageal reflux.Respirology. 2011; 16: 645-652Crossref PubMed Scopus (51) Google Scholar, 8Kahrilas P.J. Altman K.W. Chang A.B. et al.Chronic cough due to gastroesophageal reflux in adults: CHEST guideline and expert panel report.Chest. 2016; 150: 1341-1360Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 9Smith J.A. Decalmer S. Kelsall A. et al.Acoustic cough-reflux associations in chronic cough: potential triggers and mechanisms.Gastroenterology. 2010; 139: 754-762Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar Further confusing the picture, conditions associated with EER (such as chronic cough) may cause GERD or increase reflux episodes.10Rangan V. Borges L.F. Lo W.K. et al.Novel advanced impedance metrics on impedance-pH testing predict lung function decline in idiopathic pulmonary fibrosis.Am J Gastroenterol. 2022; 117: 405-412Crossref PubMed Scopus (6) Google Scholar Approaching these conditions with such knowledge will enable a more comprehensive approach to evaluation and management between disciplines. Ultimately, a large differential of possible EER syndromes should be entertained because EER may only be a part of the equation.11House S.A. Fisher E.L. Hoarseness in adults.Am Fam Physician. 2017; 96: 720-728PubMed Google Scholar Table 1 includes potential manifestations of EER, a non-exhaustive list of non-EER/non-gastroenterology differential diagnoses, and potential multidisciplinary teams for collaborative evaluation. Best Practice Advice 3: Currently, there is no single diagnostic tool that can conclusively identify GER as the cause of EER symptoms. Determination of the contribution of GER to EER symptoms should be based on the global clinical impression derived from patients' symptoms, response to GER therapy, and results of endoscopy and reflux testing. Although various diagnostic tests are available to evaluate GERD, there is not a single gold standard test for the diagnosis of EER. Instead, a diagnosis of EER requires incorporating the global clinical evaluation involving patients' symptoms, endoscopic findings, esophageal reflux monitoring, and response to treatments.1Katz P.O. Dunbar K.B. Schnoll-Sussman F.H. et al.ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease.Am J Gastroenterol. 2022; 117: 27-56Crossref PubMed Scopus (145) Google Scholar,12Gyawali C.P. Kahrilas P.J. Savarino E. et al.Modern diagnosis of GERD: the Lyon consensus.Gut. 2018; 67: 1351-1362Crossref PubMed Scopus (700) Google Scholar Further adding to the challenge is that there is limited accuracy of tests when it comes to determining the causal association of GERD and extraesophageal symptoms. Pragmatically, the exclusion of GERD decreases the chance that extraesophageal symptoms are caused by GERD. On the other hand, if a GERD diagnosis can be objectively supported, the possibility remains that GERD may be a causal factor for symptoms. Recognizing the potential pros and cons of various diagnostic tests facilitates their application to diagnosing GERD and attributing GERD to extraesophageal symptoms. Determination of GERD contribution should be personalized to the individual patient and should take into account patient symptoms, response to GERD treatment, and objective evidence of GERD on endoscopic or reflux testing. Best Practice Advice 4: Consideration should be given toward diagnostic testing for reflux before initiation of proton pump inhibitor (PPI) therapy in patients with potential extraesophageal manifestations of GERD, but without typical GERD symptoms. Initial single-dose PPI trial, titrating up to twice daily, in those with typical GERD symptoms is reasonable. Best Practice Advice 5: Symptom improvement of EER manifestations while on PPI therapy may result from mechanisms of action other than acid suppression and should not be regarded as confirmation for GERD. The limitations of an empiric PPI trial in diagnosis of EER are due to the inconsistent therapeutic response of EER-associated syndromes to PPI (pharmacologic management). A meta-analysis demonstrated sensitivity of 71%–78% and specificity of 41%–54% for an empiric PPI trial (as compared with esophagitis on endoscopy or ambulatory pH monitoring) among patients with classic reflux symptoms of heartburn and regurgitation.13Numans M.E. Lau J. de Wit N.J. et al.Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics.Ann Intern Med. 2004; 140: 518-527Crossref PubMed Scopus (295) Google Scholar Considering the greater variation expected with PPI response for extraesophageal symptoms, the diagnostic performance of empiric PPI trial for a diagnosis of EER would be anticipated to be substantially lower. Furthermore, symptom response to PPI suggests reflux as a contributor; however, this should not be taken as confirmation of GERD because of possible placebo effects.14Dent J. Vakil N. Jones R. et al.Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: the Diamond Study.Gut. 2010; 59: 714-721Crossref PubMed Scopus (239) Google Scholar With potential drawbacks of PPI (costs, rare adverse events) and limited evidence for a PPI trial for diagnosing GERD-related EER, consideration should be given for early reflux testing instead of empiric PPI therapy in patients without typical reflux symptom (Figure 1). Thus, although there is clinical value in incorporating response to PPI treatment, its isolated application does not support or refute an EER diagnosis or long-term treatment. Esophagogastroduodenoscopy (EGD) and laryngoscopy have limited roles in the diagnosis of EER (see Supplementary Material). Best Practice Advice 6: In patients with suspected extraesophageal manifestation of GERD who have failed one trial (up to 12 weeks) of PPI therapy, one should consider objective testing for pathologic GER, because additional trials of different PPIs are low yield. Best Practice Advice 7: Initial testing to evaluate for reflux should be tailored to patients' clinical presentation and can include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive medications. Best Practice Advice 8: Testing can be considered for those with an established objective diagnosis of GERD who do not respond to high doses of acid suppression. Testing can include pH impedance monitoring while on acid suppression to evaluate the role of ongoing acid or non-acid reflux. Ambulatory esophageal reflux monitoring provides a method to quantitate esophageal reflux burden to facilitate an objective GERD diagnosis, particularly in the setting of non-erosive reflux disease. Recent recommendations toward ambulatory reflux testing before initiation of empiric pharmacotherapy in patients with EER symptoms were guided by the fact that 50%–60% of patients with EER symptoms will not have GERD and will not respond to anti-reflux therapies, as well as cost-effective studies favoring early testing with reflux monitoring over empiric PPI trial in EER.15Kleiman D.A. Beninato T. Bosworth B.P. et al.Early referral for esophageal pH monitoring is more cost-effective than prolonged empiric trials of proton-pump inhibitors for suspected gastroesophageal reflux disease.J Gastrointest Surg. 2014; 18 (discussion 34): 26-33Crossref PubMed Scopus (8) Google Scholar, 16Carroll T.L. Werner A. Nahikian K. et al.Rethinking the laryngopharyngeal reflux treatment algorithm: evaluating an alternate empiric dosing regimen and considering up-front, pH-impedance, and manometry testing to minimize cost in treating suspect laryngopharyngeal reflux disease.Laryngoscope. 2017; 127: S1-S13Crossref PubMed Scopus (38) Google Scholar, 17Gyawali C.P. Carlson D.A. Chen J.W. et al.ACG clinical guidelines: clinical use of esophageal physiologic testing.Am J Gastroenterol. 2020; 115: 1412-1428Crossref PubMed Scopus (68) Google Scholar Several modalities are available for ambulatory esophageal reflux monitoring that include a catheter-based pH sensor, pH impedance, or wireless pH capsule (Table 2). Each testing modality, as well as testing on or off acid suppressive therapy, offers advantages and disadvantages in clinical practice (see Supplementary Material).Table 2Modalities of Ambulatory Esophageal Reflux MonitoringpH impedancepH catheterWireless pH capsuleStandard distal pH sensor positioning5 cm proximal to LES (manometrically identified)5 cm proximal to LES (manometrically identified)6 cm proximal to SCJ (endoscopically identified)Test duration24 hours24 hours48–96 hoursTest settingPlaced in awake patientPlaced in awake patientTypically placed during sedated endoscopyReflux composition detectedAcidic, weak-acidic, non-acidicAcidicAcidicProximal reflux detected?YesPossibleNoLES, lower esophageal sphincter; SCJ, squamocolumnar junction. Open table in a new tab LES, lower esophageal sphincter; SCJ, squamocolumnar junction. Ambulatory esophageal pH monitoring objectively defines reflux burden to facilitate a GERD diagnosis but does not determine if GERD is the cause of extraesophageal symptoms. Whichever the reflux testing modality, the strongest confidence for EER is achieved after ambulatory reflux testing showing pathologic acid exposure and a positive symptom-reflux association for EER symptoms. The pH impedance monitoring can detect weakly acidic and non-acidic reflux episodes (in addition to acid reflux), as well as proximal reflux episodes, which may cause extraesophageal symptoms by direct acid-mucosal contact. Notably, ambulatory reflux monitoring for the evaluation of GERD in the presence of extraesophageal symptoms should be performed off acid suppressive therapy, unless previous objective evidence (eg, positive pH test) for GERD exists (Figure 1). Best Practice Advice 9: Alternative treatment methods to acid suppressive therapy (eg, lifestyle modifications, alginate-containing antacids, external upper esophageal sphincter compression device, cognitive-behavioral therapy, neuromodulators) may serve a role in management of EER symptoms. Treatment of esophageal and extraesophageal GERD aims to achieve and maintain symptom relief, heal mucosal damage, and prevent complications. Treatment strategies include lifestyle measures, pharmacologic management of reflux through alginates or acid suppression, a device to prevent supra-esophageal reflux by bolstering the upper esophageal sphincter, and surgical/endoscopic approaches to augment the anti-reflux barrier at the level of the lower esophageal sphincter. Ascertaining the effectiveness of EER therapies is challenging, because in the absence of a gold standard diagnostic test that can reliably identify patients in whom extraesophageal symptoms are due to GERD, clinical trials may often include patients in whom GERD is not the cause of the symptoms, and in whom consequently therapy will fail. Furthermore, there is heterogeneity among EER studies in patient inclusion criteria and lack of gold standards for testing and treatment regimens and endpoints.18Barrett C.M. Patel D. Vaezi M.F. Laryngopharyngeal reflux and atypical gastroesophageal reflux disease.Gastrointest Endosc Clin N Am. 2020; 30: 361-376Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 19Cosway B. Wilson J.A. O'Hara J. The acid test: proton pump inhibitors in persistent throat symptoms—a systematic review of systematic reviews.Clin Otolaryngol. 2021; 46: 1263-1272Crossref PubMed Scopus (2) Google Scholar, 20Lechien J.R. Saussez S. Schindler A. et al.Clinical outcomes of laryngopharyngeal reflux treatment: a systematic review and meta-analysis.Laryngoscope. 2019; 129: 1174-1187Crossref PubMed Scopus (99) Google Scholar These issues may in part explain the limited response to treatment in the studies that are discussed in this section. Lifestyle modification measures including avoidance of refluxogenic foods, food avoidance for at least 2–3 hours before recumbency, positional changes during the sleep period, and weight loss have been proposed for management of GERD.1Katz P.O. Dunbar K.B. Schnoll-Sussman F.H. et al.ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease.Am J Gastroenterol. 2022; 117: 27-56Crossref PubMed Scopus (145) Google Scholar Late evening meals have been shown to contribute to reflux.21Ness-Jensen E. Hveem K. El-Serag H. et al.Lifestyle intervention in gastroesophageal reflux disease.Clin Gastroenterol Hepatol. 2016; 14: 175-182 e1–e3Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar Head of bed elevation as well as left lateral decubitus position have been shown to improve nocturnal esophageal acid exposure.22Khan B.A. Sodhi J.S. Zargar S.A. et al.Effect of bed head elevation during sleep in symptomatic patients of nocturnal gastroesophageal reflux.J Gastroenterol Hepatol. 2012; 27: 1078-1082Crossref PubMed Scopus (67) Google Scholar, 23Schuitenmaker J.M. van Dijk M. Oude Nijhuis R.A.B. et al.Associations between sleep position and nocturnal gastroesophageal reflux: a study using concurrent monitoring of sleep position and esophageal pH and impedance.Am J Gastroenterol. 2022; 117: 346-351Crossref PubMed Scopus (13) Google Scholar, 24Person E. Rife C. Freeman J. et al.A novel sleep positioning device reduces gastroesophageal reflux: a randomized controll